This project is to determine the molecular basis of how sympathetic nerves extend axons along the vasculature with the goal of innervating their target organs. To study this, we use coronary vasculature model as a favorable model system. We discovered a reciprocal guidance event in the patterning of sympathetic nerves in the developing heart. Our whole-mount imaging revealed that the pattern of large-diameter coronary veins influences the pattern of sympathetic innervation in the heart. Further genetic studies and in vitro organ culture experiments demonstrated that coronary veins serve as an intermediate template that guides distal sympathetic axon projection via local secretion of NGF by coronary vascular smooth muscle cells (manuscript in revision for publication). This coordinated process ultimately allows topological targeting of axons to final targets such as coronary arteries and cardiac conduction system. Our results suggest that target organs possess unique and stereotypical patterns of innervation, mediated by tissue substructures, such as coronary veins in the heart, that are adapted to complex organ structure and physiology.